Correlation between circulating fibrosis biomarkers with left atrial function and left atrial volume index in rheumatic mitral stenosis.

Mitral stenosis is the most common rheumatic heart disease (RHD) disorder worldwide, including in Indonesia. This pathological condition causes left atrial pressure, leading to left atrial fibrosis that affects the structure and function of the left atrial as well as the clinical condition. The aim of this study was to assess the correlation between circulating fibrosis biomarkers with net atrioventricular compliance (Cn) as a parameter of left atrial function, and left atrial volume index (LAVI) as a parameter left atrium structure of changes. A cross-sectional study was conducted at Panti Rahayu Hospital and Permata Bunda Hospital, Purwodadi, Central Java, with a total of 40 RHD patients with severe mitral stenosis. The ELISA was used to measure the levels of carboxy-terminal propeptide of type I procollagen (PICP), matrix metalloproteinase I (MMP-1), tissue inhibitor matrix metalloproteinase 1 (TIMP-1), and transforming growth factor-ß1 (TGF-ß1). The left atrial function was assessed by measuring Cn, and the LAVI parameters were measured to assess left atrium structure/size. The mean levels of circulating fibrosis biomarkers were as follows: PICP 153.96±89.12 ng/mL; MMP-1 1.44±2.12 ng/mL; MMP-1/TIMP-1 ratio 0.38±0.54 and TGF-ß1 2.66±1.96 pg/mL. From the echocardiographic evaluation, the mean Cn was 5.24±1.93 mL/mmHg and the mean LAVI was 152.55±79.36 mL/m2. There were significant correlation between MMP-1 and MMP-1/TIMP-1 ratio with Cn (r=0.345 and r=0.333, respectively; both had p<0.05). PICP and TGF-ß1 biomarkers did not significantly correlate with Cn (p>0.05). Meanwhile, none of the biomarkers had a significant correlation with LAVI (p>0.05). This study highlights that MMP-1 and MMP-1/TIMP-1 ratio are potentially to be used as markers to determine the Cn in RHD patients with severe mitral stenosis. However, further studies with a higher sample size are needed to confirm this finding.

Improvement of renal functions in mice with septic acute kidney injury using secretome of mesenchymal stem cells.

Background: A potentially fatal complication of sepsis is septic acute kidney injury. Stem cell therapy is a potential new method of treating sepsis and has been applied to treat some human diseases. Objectives: This study investigated the effects of secretome-MSCs on NGAL, CRP, NF-κB, and MMP-9 proteins, and histopathology in mice with septic AKI. Methods: A post-test-only group design was conducted in 30 Balb/C male mice, which were randomly assigned to five groups: the control group was intraperitoneally injected with 0.5 ml of 0.9 % NaCl, the septic AKI, and the treatment groups (T1, T2, and T3) were intraperitoneally injected with 0.5 ml of 0.9 % NaCl and 0.3 mg/kg BW LPS single dose for three days. Three-day treatments of 150, 300, and 600 µl secretome-MSCs were administered intraperitoneally into the treatment groups. Furthermore, kidney and blood samples were collected for biochemical and histopathological analyses. Results: The T1, T2, and T3 groups had lower expression of NF-κB and MMP-9 and significantly lower CRP and NGAL levels than that of septic AKI group. T1 (1.21 ± 0.19), T2 (0.75 ± 0.22), and T3 (0.38 ± 0.14) groups demonstrated lower average scores for inflammation, necrosis, hemorrhage, and degeneration compared to septic AKI group (2.17 ± 0.13). Conclusions: Administration of 600 µl/20 g BW secretome-MSCs suppresses NF-κB and MMP-9 expression and reduces CRP and NGAL levels. Meanwhile, the 150 and 300 µl/20 g BW doses also indicated a greater improvement in renal tissue damage of mice with septic AKI.

Dose-response effect of L-citrulline on skeletal muscle damage after acute eccentric exercise: an in vivo study in mice.

Background: Eccentric exercise may trigger mechanical stress, resulting in muscle damage that may decrease athletic performance. L-citrulline potentially prevents skeletal muscle damage after acute eccentric exercise. This study aimed to assess the dose-response effect of L-citrulline as a preventive therapy for skeletal muscle damage in mice after acute eccentric exercise. Methods: This is a controlled laboratory in vivo study with a post-test-only design. Male mice (BALB/c, n = 25) were randomized into the following groups: a normal control (C1) (n = 5); a negative control (C2) with downhill running and placebo intervention (n = 5); treatment groups: T1 (n = 5), T2 (n = 5), and T3 (n = 5), were subjected to downhill running and 250, 500, and 1,000 mg/kg of L-citrulline, respectively, for seven days. Blood plasma was used to determine the levels of TNNI2 and gastrocnemius muscle tissue NOX2, IL-6, and caspase 3 using ELISA. NF-κB and HSP-70 expressions were determined by immunohistochemistry. Results: Skeletal muscle damage (plasma TNNI2 levels) in mice after eccentric exercise was lower after 250 and 500 mg/kg of L-citrulline. Further, changes in oxidative stress markers, NOX2, were reduced after a 1,000 mg/kg dose. However, a lower level of change has been observed in levels of cellular response markers (NF-κB, HSP-70, IL-6, and caspase 3) after administration of L-citrulline doses of 250, 500, and 1,000 mg/kg. Conclusion: L-citrulline may prevent skeletal muscle damage in mice after acute eccentric exercise through antioxidant effects as well as inflammatory and apoptotic pathways. In relation to dose-related effects, it was found that L-citrulline doses of 250, 500, and 1,000 mg/kg significantly influenced the expression of NF-κB and HSP-70, as well as the levels of IL-6 and caspase 3. Meanwhile, only doses of 250 and 500 mg/kg had an impact on TNNI2 levels, and the 1,000 mg/kg dose affected NOX2 levels.

Effect of Dapagliflozin on Patients with Rheumatic Heart Disease Mitral Stenosis.

(1) Background: Mitral stenosis is the most common rheumatic heart disease (RHD). Inflammation and fibrosis are the primary pathophysiology, resulting in left atrial stress and dysfunction. Dapagliflozin is a new heart failure treatment with anti-inflammation and anti-fibrosis effects from previous studies. However, the specific role of dapagliflozin in RHD mitral stenosis is unknown. This study aims to investigate (i) the effect of dapagliflozin on biomarkers of fibrosis, NT-pro BNP levels and left atrial function; (ii) the relationship between the changes in fibrosis biomarkers with left atrial function and NT-pro BNP levels. (2) Methods: An open-label randomized study was conducted on 33 RHD mitral stenosis patients divided into a dapagliflozin group which received 10 mg dapagliflozin and standard therapy, and a control group which only received standard therapy. All patients were examined for levels of PICP, MMP-1/TIMP-1 ratio, TGF-ß1, NT-proBNP, mitral valve mean pressure gradient (MPG), and net atrioventricular compliance (Cn) pre- and post-intervention. (3) Results: This study found a significant increase in PICP and TGF-ß1 and a reduction in the MMP-1/TIMP-1 ratio in the dapagliflozin group and the control group (p < 0.05). In the dapagliflozin group, the levels of NT-pro BNP decreased significantly (p = 0.000), with a delta of decreased NT-pro BNP levels also significantly greater in the dapagliflozin group compared to the control (p = 0.034). There was a significant increase in Cn values in the dapagliflozin group (p = 0.017), whereas there was a decrease in the control group (p = 0.379). Delta of changes in Cn values between the dapagliflozin and control groups also showed a significant value (p = 0.049). The decreased MPG values of the mitral valve were found in both the dapagliflozin and control groups, with the decrease in MPG significantly greater in the dapagliflozin group (p = 0.031). There was no significant correlation between changes in the value of fibrosis biomarkers with Cn and NT-pro BNP (p > 0.05). (4) Conclusions: This study implies that the addition of dapagliflozin to standard therapy for RHD mitral stenosis patients provides benefits, as evidenced by an increase in net atrioventricular compliance and decreases in the MPG value of the mitral valve and NT-pro BNP levels (p < 0.05). This improvement was not directly related to changes in fibrosis biomarkers, as these biomarkers showed ongoing fibrosis even with dapagliflozin administration.

The Role of Asiatic Acid in Preventing Dental Pulp Inflammation: An in-vivo Study.

Purpose: Acute dental pulp inflammation necessitates early treatment to alleviate inflammation and pain. In the inflammatory phase, a substance is required to lower the inflammatory mediators and reactive oxygen species that play a crucial role in that phase. Asiatic acid is a natural triterpene obtained from the Centella asiatica plant with a high antioxidant value. This study examined the effect of Asiatic acid's antioxidant, anti-inflammatory, and antinociceptive properties on dental pulp inflammation. Methods: The research is an experimental laboratory, with a post-test only with a control group design. The study utilised 40 male Wistar rats weighing 200-250 grams and aged 8-10 weeks. Rats were divided into five groups (control, eugenol, Asiatic Acid 0.5%; 1%; 2% group). Dental pulp inflammation was created in the maxillary incisor after six hours of administration of lipopolysaccharides (LPS). The dental pulp treatment then continued with the administration of eugenol and three different Asiatic acid concentrations (0.5%, 1% and 2%). In the next 72 hours, the teeth were biopsied, and the dental pulp was analysed using the enzyme-linked immunosorbent assay (ELISA) to measure the level of MDA, SOD, TNF-α, beta-endorphins and CGRP. Histopathological examination and the Rat Grimace Scale were utilised to determine the level of inflammation and pain, respectively. Results: The effect of Asiatic Acid on MDA, TNF-α, and CGRP levels decreased significantly compared to the control group (p=<0.001). On the SOD and beta-endorphin levels, Asiatic acid treatment resulted in a considerable rise (p =<0.001). Conclusion: Due to its antioxidant, anti-inflammatory, and antinociceptive characteristics, Asiatic acid can reduce inflammation and pain in acute pulp inflammation due to its ability to decrease MDA, TNFα, and CGRP levels while raising SOD and beta-endorphin levels.

Association between carotid intima media thickness and acute ischemic stroke at an Indonesian tertiary referral hospital.

Objectives: A high prevalence of tobacco smoking contributes to a high incidence of acute ischemic stroke (AIS) in Indonesia. Large-artery atherosclerosis is known to be a significant cause of AIS. The present study was aimed at evaluating the association between AIS and atherosclerosis on the basis of carotid intima-media thickness (CIMT) measurements in a tertiary care hospital in Indonesia. Methods: A total of 79 patients with AIS (case study group) and 79 individuals without AIS (control group) were included. Chi-squared tests and odds ratios were used to compare the groups and determine associations. We also considered factors such as age, body mass index (BMI), sex, type-2 diabetes mellitus (T2DM), hypertension, smoking status, dyslipidemia, socioeconomic status, and educational level in the statistical analyses. A p-value <0.05 was considered statistically significant. Results: Stratification of atherosclerosis into case study and control groups with respect to all study variables indicated a significant relationship (p > 0.05) between atherosclerosis and all variables except low socioeconomic status (p = 0.265) and low educational level (p = 0.180). Regression analysis demonstrated that a BMI ≥25 kg/m2, compared with a normal BMI, was associated with a 2.139-fold higher risk of atherosclerosis. Conclusions: AIS was associated with atherosclerosis, on the basis of CIMT measurements, according to age, BMI, sex, T2DM, hypertension, smoking status, dyslipidemia, socioeconomic status, and education level in the Indonesian population.

Exosomes Derived from Secretome Human Umbilical Vein Endothelial Cells (Exo-HUVEC) Ameliorate the Photo-Aging of Skin Fibroblast.

Purpose: This is an in-vitro experimental study to analyze the effect of Exo-HUVEC on endothelial cell (CD31), cell proliferation, matrix metalloproteinase 1 (MMP-1) and collagen type 1 on irradiated fibroblast with UVB as photo-aging model. Patients and Methods: Fibroblast cultures were divided into 5 groups, namely without UVB exposure, UVB exposure 600mJ/cm2 for 80 seconds as photo-aging model, and UVB exposure +Exo-HUVEC exposure 0.1%, 0.5% and 1%. The endothelial cell was stained with a CD31 marker, MMP-1 were examined with ELISA, cell proliferation is detected using an MTT assay; meanwhile, collagen type 1 deposition and endothelial cell were measured using flowcytometry. Results: This study found positive endothelial cell marker CD31. Significant difference was found in cell proliferation, MMP-1 and collagen type 1 level between the control group with UVB irradiation and the treatment group with Exo-HUVEC (p < 0.05). Conclusion: Exo-HUVEC significantly increases cell proliferation and collagen type 1 level, while decrease MMP-1 levels on irradiated fibroblast; therefore, Exo-HUVEC ameliorate the photo-aging of skin fibroblast.